When it rains it pours, as they say.
Yes, sometimes there's so much going on that I can't possibly blog about it all, particularly now that I've cut back a bit. This week seems to be turning into one of those weeks. Yesterday, I couldn't resist having a bit of fun with the grande dame of the anti-vaccine movement, Barbara Loe Fisher when she released a seriously hypocritical and silly press release whining about how mistreated she thinks her organization, the Orwellian-named National Vaccine Information Center (NVIC) has been because the American Academy of Pediatrics (AAP) had the audacity to--gasp!--write a letter to Delta Airlines complaining about its airing of an NVIC video about the flu vaccine that was cleverly packed with subtle misinformation topped off with a link to the NVIC website and its cornucopia of anti-vaccine canards. However, to have that bit of fun, I had to put off blogging about another hilariously off-base bit of pseudoscience from the anti-vaccine movement, this time courtesy of everyone's favorite promoter of quackery on the Internet (with the possible exception of Mike Adams), "Dr." Joe Mercola. So what's Mercola up to this time? This time, he's flogging another bit of anti-vaccine pseudoscience on his blog in a post entitled Is Alarming Rise in Autism Linked to 1988 Event? I could just answer Mercola's question by saying no, but I was curious what he was talking about, which is always my downfall (or at least the downfall of some of my neurons, which inevitably undergo apoptosis when exposed to the burning stupid that the anti-vaccine movement is capable of). I had to suffer; so I figured I'd make my readers suffer through it too, the difference being that I can usually make it entertaining.
So let's see what Mercola is talking about:
In 1988, the first conjugate vaccine was approved for use in the U.S.It was intended to protect infants and young children against Haemophilus influenzae type b (Hib); a bacterial infection that can lead to pneumonia, infections of your blood, joints, bones, and pericardium.
Historically, it has also been a leading cause of bacterial meningitis.
Since that time, the vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively.
Starting in the late 1980's, there was a marked increase in the reported prevalence of autism spectrum disorders among children in the U.S.
A similar increase was seen in Denmark and Israel.
Do I smell a post hoc ergo propter hoc fallacy here? Is there a correlation between global warming and the decreasing number of pirates in the world? But rather than wasting too much time with Mercola's credulous regurgitation of this alleged study, let's find the study itself. This isn't too difficult because, unlike a lot of cranks, Mercola is actually kind enough to provide a link to the study, which is by someone named Brian J. Richmand and entitled Hypothesis: Conjugate vaccines may predispose children to autism spectrum disorders.
"Hypothesis"? As Scooby-Doo would say, "Ruh-roh, Raggy."
It looks as though this particular "study" is in the crank journal Medical Hypotheses (MH). It's been a while since I've written about this particular journal; so let's take a brief trip down memory lane. MH has "distinguished" itself from other medical and scientific journals in its willingness to publish things such as a "hypothesis" by autism quacks Mark and David Geier that provided the basis for their use of chemical castration to treat "vaccine-induced" autism, a "hypothesis" claiming that antiperspirants cause breast cancer, a "hypothesis" by prominent anti-vaccine activists that thimerosal in vaccines causes autism, as well as other hypotheses claiming that masturbation is a treatment for nasal congestion or that high-heeled shoes are linked to schizophrenia. Finally, MH went one bizarre hypothesis too far when it published an article by arch-HIV/AIDS denialist Peter Duesberg that was so beyond the pale that it was too much for Elsevier, the publisher of MH, which finally told then-editor Bruce Charlton that enough's enough. After Elsevier declined to renew Charlton's contract, I was curious what would become of MH, given that MH's--shall we say?--openness to virtually any hypothesis, no matter how wacky and how without a basis in science derived mainly from Charlton's editorial philosophy. Don't get me wrong. As I've pointed out, I always thought that there was a place in the medical literature for a journal devoted to exploring highly speculative hypotheses, but the problem with MH is that it became a magnet for cranks and, because it was listed in PubMed, it was easy for cranks to represent it as a legitimately peer-reviewed journal and cite its articles even though Charlton admitted that it wasn't peer-reviewed.
It would appear that the editorial standards under the new regime are the same as they were under the old regime. In other words, meet the new boss, same as the old boss. At least this article would seem to argue that that's the case. Let's go to the abstract:
The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively.
There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae.
Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides with the intense myelination process in infants and young children, and conjugate vaccines may have disrupted evolutionary forces that favored early brain development over the need to protect infants and young children from capsular bacteria.
First off, this is the first time I've seen an anti-vaccine advocate try to link the Hib vaccine to autism. Maybe I live a sheltered life (although I doubt it, given how much I dive into the writings of anti-vaccine advocates and various anti-vaccine websites). Be that as it may, the Hib vaccine is an incredible vaccine that has made an enormous impact in a brief 20 years or so. Before the Hib vaccine, pediatricians would dread seeing children in the emergency room with Hib because it could cause such serious disease and even death. Hib was a pediatrician's nightmare. Since the Hib vaccine hit the market, incidence and morbidity from Hib have plummeted, and most pediatricians who trained after the early 1990s have never seen a case of bacterial meningitis, pneumonia, or epiglottitis due to Hib. This is the good that the Hib vaccine has done.
As for this "paper," well, let's just say that it's rampant speculation with no evidence based on confusing correlation with causation. Actually, it doesn't even make a particularly convincing case for a correlation. In the process, Richmand abuses evolution as a way of "explaining" why conjugated vaccines like the Hib vaccine could cause autism. As lawyers would say, Richmand uses a lot of facts not in evidence to try to convince the gullible that his hypothesis (and it's really a stretch to call it that, given that real scientific hypotheses are generally supported by enough data to make them plausible and worth expending the time and resources to test). Why the lawyer crack? Because it appears that Richmand is not a scientist but rather a lawyer.
As is pointed out, the Hib vaccine was first approved in the U.S. in 1988 for infants starting at age 15 months, and in late 1990 was approved for use in infants aged two months. The vaccine was later approved in Denmark in 1993 and Israel in 1992, later becoming part of the recommended slate of vaccines administered through Israel's national health care system in 1994. One can't help but sense a bit of cherry picking of nations here. What about the many European nations other than Denmark that introduced the Hib vaccine into their childhood immunization schedules around the same time? If I were an anti-vaccine advocate and wanted to make a powerful case for a correlation between a vaccine like Hib and any condition, be it autism, neurodevelopmental problems, or whatever, I'd look at data from as many nations as I could. It's not just the U.S., for instance, that has data regarding autism prevalence for birth cohorts from that period of time. Instead, Richmand picks three countries. One also can't help but notice that two of these countries are ones where large studies were performed to demonstrate no correlation between thimerosal-containing vaccines and autism, in particular the Danish studies, which were among the earliest large, well-designed studies that failed to find a correlation between thimerosal and autism.
In any case, it's interesting to note that there are no graphs and no statistics presented to demonstrate that there even is a correlation between increases in autism prevalence and the introduction of the Hib vaccine into the U.S., Denmark, and Israel, but if you really want to know how bad Richmand's speculations are, look no further than this passage:
Using regression analysis, McDonald and Paul then sought to determine (at a 95% confidence interval) the existence of a change-point in the cumulative incidence for autism disorder in the birth cohorts covered in each of the 3 selected studies, as well as for their worldwide data set. A change-point was calculated for both the California and Danish studies at 1987.5 (95% CI: 1987- 1988) and for the combined worldwide data set at 1988.7 (95% CI: 1985.9-1991.8). No change-point could be calculated for the Kohoku Ward, Japan data set, but the incidence of autism disorder increased steadily for the 1988 through 1996 birth cohorts. Inasmuch as data collection was not started in the Kohoku Ward study until 1988, the absence of a change-point in the Kohoku Ward data is consistent with the findings of the 1987.5 change-points for the California and Denmark data sets and the 1988.7 change-point for the worldwide data set.
It should also be noted that the change-point calculated by McDonald and Paul for the California data set for autism disorder is consistent with the previously discussed findings regarding combined ASDs among US school-aged children based on administrative data. Also of interest with regard to this hypothesis are comparative graphs presented by McDonald and Paul showing the rise in rates of autism disorder in the US and Denmark. Although McDonald and Paul calculated an identical change-point for both countries, these graphs indicate that the initial increase in autism disorder rates in Denmark was relatively modest and the preponderance of the increase in Danish autism disorder rates lagged the increase in the California study by several years.
I thought this study sounded familiar; so I did a quickie search of my blog archives, and, lo and behold, it turns out that I've blogged about this study before. Basically, it's a pretty lousy study that used questionable statistical methodology in order to identify what its authors considered to be "change points" or inflections in the incidence curve over time using three studies, one in Japan, one in the U.S., and one from Denmark. An anti-abortion group jumped all over it and claimed to correlate various "change points" with the introduction of vaccines containing "fetal parts." (I kid you not; I really can't make stuff like this up.) Of course, there is a problem. In the U.S. study the change point identified occurred in 1987, before the introduction of the Hib conjugate vaccine into widespread use in the U.S.. Ditto Denmark, where the change point was also 1987 and, supposedly the change point for the world was 1988, although I never figured out how one could say that from just three studies in three nations. Be that as it may, this study is pretty darned thin gruel to conclude anything about autism incidence and whether there were "environmental triggers" introduced 23 years ago that caused inflections in the autism incidence curve.
As for the rest of the arguments Richmand makes, he really stretches to try to make a correlation. The funny thing is, though, that even if the McDonald study were correct, it would undermine Richmand's hypothesis because his hypothesis would predict that autism incidence would take off two or three years after the introduction of the Hib vaccine in a nation for infants (i.e., the dose at two months). That would mean, in the U.S. at least, late 1993 at least. In any case, no such increases appear to correlate very closely with the introduction of Hib in any of the countries examined other than in a vague, general way. More importantly, the introduction of the broadened diagnostic criteria in the DSM-IV introduced in 1994 (in the U.S.) and 1996 (in Europe) rears its ugly head again for those determined to confuse correlation with causation; i.e., anti-vaccinationists. To paper over that hole in his hypothesis, Richmand starts blaming efforts to increase the immunogenicity of the vaccine through the 1990s and changes in time of the protein carrier used in the vaccine and then the approval of the pneumococcal vaccine in 2000.
Starting with a weak to nonexistent association, what does an MH author do? He gets out a shovel and digs deeper, this time invoking immunology to try to explain why conjugated vaccines are different (and presumably cause teh autism). He goes on and on about differences in B-cell and T-cell responses elicited by carbohydrates:
Although conjugate vaccines are truly life saving, these vaccines by-pass important immunological regulatory mechanisms and, consequently, deserve careful retrospective scrutiny. In the absence of conjugate vaccines, B cells with an affinity for carbohydrate antigens are carefully regulated in order to prevent autoimmunity [30-32]. Because antibodies produced against carbohydrate antigens (including the Hib capsule) are often intrinsically autoreactive with self-carbohydrates, differentiation of these B cells into B2 cells may lead to autoimmunity [30-32]. Antibody to self-carbohydrates has been associated with several autoimmune disorders, including systemic lupus erythematosus [30,31], myocarditis and rheumatic heart [36], Sydenham's chorea [37], and pediatric neuropsychiatric disorder associated with Streptococcus (PANDAS) [38]. Unlike antibodies produced by B2 cells, the shorter-lived, lower affinity antibodies produced by B1 and MZB cells are less likely to lead to autoimmunity [30,36].
Of course, no strong evidence is presented that any of these immunological changes have anything to do with the pathogenesis of autism, but none of this stops Richmand from invoking an evolutionary basis for these immune responses and doing more handwaving about how they might be relevant to autism:
The hypo-responsiveness of the immune systems of infants and young children to capsular bacteria is unexpected from an evolutionary perspective. In addition to the inability of infants and young children to mount an effective TI immune response to capsular bacteria, IgM and IgG2 do not readily cross the placenta [5,40], suggesting that fetuses also may not be well protected from capsular bacteria. The vulnerability of infants, young children, and possibly fetuses to capsular bacteria would appear to create a significant evolutionary disadvantage.
These multiple limitations on the presence of antibody to carbohydrate antigens in fetuses, infants, and young children raise the question of whether there is a countervailing evolutionary advantage to these limitations. One possible explanation is that antibody to carbohydrate antigens may be cross-reactive with neural glycoproteins between protection against capsular bacteria and the need for neural development.
This possibility is consistent with the fact that myelination occurs in stages from infancy through at least early childhood [34], which appears to coincide with the period during which the immune system is hypo-responsive to carbohydrate antigens. Moreover, the period during which the immune system is least responsive to carbohydrate antigens corresponds to the period of most intense myelination. Viewed in this context, it is possible that not only is antibody to carbohydrates deleterious to neural development in infants and young children, but their negative effects are enhanced by the robust TD immune responses induced by conjugate vaccines. The balance struck through evolution may have been significantly disrupted through the introduction of conjugate vaccines for infants and young children (Chart 2).
Even if all of this were true, it would say nothing about whether Richmand's hypothesis were reasonable, because for Richmand's hypothesis to be worth exploring, there would have to be a real correlation between the introduction of the Hib vaccine and an increase in the incidence of autism. Quite simply, he doesn't make the case that there is.
Now, I know what you're probably thinking. You're probably thinking: This is MH. What did you expect? Fair enough. I was more interested in whether MH had cleaned up its act after the ouster of Bruce Charlton as its editor. Clearly, it hasn't, and the new regime has apparently happily published more fodder for the anti-vaccine movement, so much so that an outrageously credulous accompanying editorial by Noel R. Rose of the Johns Hopkins University School of Medicine. Dr. Rose appears to be a bit on the edge as far as anti-vaccine beliefs go, at least if his editorial Conjugate vaccines and autism is any indication. Either that, or Dr. Rose is so open-minded that he's allowed his brains to fall out, given that in his editorial he praises Richmand as an example of noncientist "original thinkers who do not have the standard diplomas, writing that he has "raised significant questions" and arguing that the "merits of this thoughtful hypothesis should be carefully weighed." To me, the only significant question that Richmand's article raised was how on earth MH could keep publishing such tripe after Elsevier supposedly cleaned house among its editorial staff and instituted a system of peer review and the only merit of this hypothesis that should be "carefully weighed" is whether a printout of the article would make a good lining for a bird cage. After all, if this article by Richmand is any indication, MH continues be--shall we say?--"open" to pseudoscience and willing to provide nonscientists with anti-vaccine proclivities a forum that provides them with a patina of seeming respectability plus fodder for cranks like Joe Mercola to write posts castigating vaccines. Same as it ever was.
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Totally ignoring all the rest of his nonsense, I have to seriously roll my eyes at this. Why does it have to be adaptive? Not all evolutionary changes are for the better, and something may persist not because it is helpful but because it is intrinsically related to something else that is. (There's a whole lotta code reuse in the human body, to use a software analogy. Heck, it's more than analogy -- the exact same situation occurs even in software, which really is intelligently designed; bugs often get deliberately left in if they can't be easily fixed without screwing up something else.)
Is there an evolutionary advantage to the suboptimal infant immune system? Maybe. Maybe not. One might also ask if there is a "countervailing evolutionary advantage" to eclampsia, even though left untreated (i.e. the "in the wild" condition) it is invariably fatal if the mother doesn't manage to deliver in time. There is an evolutionary advantage to sickle cell anemia, but it's not direct -- the genes that produce sickle cell anemia confer some protection against malaria, but sickle cell anemia itself is not helpful and indeed seems like a rather steep price to pay.
I dislike the assumption that if something exists, it must be evolutionary advantageous. This is not at all true, and apparently stems from an arrogant sense of man's perfection combined with a naive view that Mother Nature is beneficent. Which she definitely is not.
I have been following the great unravelling of AJW @ BMJ with great interest while observing BLF *et Cie* provide the side show -I have now arrived at a rather frightening conclusion:
the pricipals involved are in their 50s or 60s- our esteemed host is *nearly* 50. I am 50-something. The life expectancy in both the US & UK approaches 80.
This may go on until all of us are *dead*. I don't know whether to laugh or cry.
OK, I hate to always be the person throwing the proverbial monkey wrench into elegant hypotheses, but Mr. Richmond should have spent less time looking up immunology and more time looking at epidemiology.
A casual visit to the CDC website's "statistics and surveillance" section reveals the following (seriously, it took me less than five minutes to do this while I was having my coffee):
Haemophilus influenzae B vaccine coverage for those 19-35 months in 1995 (the earliest year on-line) shows that 91.2% had received three HiB vaccinations. We can safely assume that a higher percentage had received one or two vaccinations.
So why hadn't the "autism epidemic" peaked by 1995, if it was "triggered" by the conjugate HiB vaccine?
If you "fast-forward" to the 2010 results, HiB vaccination has slipped slightly so that only 89.2% had received three vaccinations in the 19-35 month group.
If Mr. Richmond objects that the 19 - 35 month group doesn't reflect the "early childhood" vaccination rate, then let's go to 1998, the first year where the survey covered 3 month-olds separately. In 1998, 85.4% of children had received one HiB vaccination by three months. In 2000, that number had risen slightly to 87.1%, 88.3% in 2005 and down (slightly) to 83.3% in 2010.
If Mr. Richmond's hypothesis was correct, the prevalence of autism sould have reached a plateau by 1995 or 1998 and remained steady - as a percentage of the population - to now. If we look at the same California DDS figures he used, the autism prevalence did not plateau by 1995 (or 1998) and has not remained steady since then.
Ergo, Mr. Richmond's hypothesis is not supported by the data. He must go sit on the "Group W" bench with Mr. Dochniak.
Prometheus
I wonder if it's possible to get 'time cube' published in there. Or this paper I've blogged about which 'proves' that the 'true' value of pi is exactly 3.125. Although, it might be inappropriate since a potential monetary reward is paid if one finds,
At least the kooks in my field are harmless.
Good article, Orac - thanks for writing it.
I think he's blaming all conjugate vaccines, of which Hib was only the first. You'd also have to take into account PCV which was added in 2001.
Given how his hypothesis already doesn't fit any data, that's probably not going to help his case either.
masturbation is a treatment for nasal congestion
Boy, that sounds promising.
Why the hell is this garbage journal listed in PubMed? Is there any way to request that it be delisted?
Unfortunately, it is not the only bovine excrement journal on PubMed. There are several devoted to alternative medicine, like "Homeopathy" and BMC Complementary and Alternative Medicine. (just do a search of any CAM on PubMed and several pop up)
I used to measure glucose and protein in CSF samples from children with suspected meningitis, starting in the early 80s, and had noticed a dramatic drop in the number of cloudy and purulent samples beginning in the 90s. I hadn't realized until recently that the HiB vaccine was responsible. It's great to see a public health measure make such a difference in my own lifetime.
If conjugate vaccines were really responsible for the increase in autism diagnoses, what do they think caused the concomitant fall in "mental retardation" diagnoses?
CG (#5):
PCV (one or more immunisations by age 3 months):
2002 - 19.8%
2003 - 57.1%
2004 - 61.7%
2005 - 73.7%
2006 - 77.7%
2007 - 81.4%
2008 - 84.0%
2009 - 83.1%
2010 - 83.5%
So, where was the plateau after 2005? According to California DDS (which also, I should note, advises that their data is not valid for year-to-year comparsons), the prevalence of autism has continued a pretty even rise to today. The same is seen in the US Dept. of Education data. No sign of "leveling off" after 2005 - or a "bump" after 2001, either.
This time it took me 7 minutes to get the data.
Mr. Richmond remains on the "Group W" bench.
Prometheus
Justicar @12:13 -- I have to take exception with your source who proves that pi is exactly 3.125. Back when I was in grad school, the town was plastered by flyers by a mathematician who had proved, to his own satisfaction at least, that pi is exactly the square root of 10.
They can't both be right, unless the square root of 10 is actually 3.125. Gosh, maybe it is!
In one of the four times my oldest son entered the emergency department at Children's because he was having difficulty breathing due to croup, a pair of doctors came in with a special tiny camera. As they put it down the throat of the very upset toddler they explained they were looking for epiglottitis, which was fairly common with haemophilus influenzae type b infections. Seeing that my son did not have it, they remarked that they were seeing less and less since the Hib vaccine became available.
That was in 1991. Which shows how fast that vaccine started to save children.
Unfortunately, the kid had more difficulty breathing and I had to get the blow-by tube with extra oxygen as I comforted him. We used to call croup the "pampering disease." It is because being upset causes greater respiratory distress.
(that same year I met a woman whose first child died from haemophilus influenzae type b, a child the same age as my oldest son... I am flabbergasted that anyone wants it to return!)
I have a comment in moderation. Since my oldest missed out on the Hib vaccine, but his little brother got it two years later in 1990.
Around that time I met one woman whose child died from haemophilus influenzae type b around 1989, and later a woman whose son almost died but ended with with seizures, a speech disorder and other learning disabilities.
I know these are just anecdotes. But I am just shocked that people think that disease should return.
other hypotheses claiming that masturbation is a treatment for nasal congestion
I've only read Ben Goldacre ridiculing the article, not the article itself -- for my university, understandably enough, does not waste money to pay for access to the Med.Hypoth. archives. But the argument is not unreasonable; sexual arousal can cause nasal congestion.
http://en.wikipedia.org/wiki/Honeymoon_rhinitis
The congestion stops when orgasm is reached and the arousal is discharged. Whether the orgasm is solitary or a collaborative endeavour is optional.
Commenters at Goldacre's blog note that blowing one's nose also works and raises fewer eyebrows on the commuter train.
@Shay (#6):
Yeah, but most people's backs don't bend that much, or their nostrils aren't big enough...
@ Prometheus:
2005 wouldn't be the plateau - you haven't accounted for the time between vaccination and diagnosis. That'd push it back to 2007ish. And an 8% increase from 2005-7 could show up in the data, so technically the plateau should start more around 2009 and might not be evident in the numbers yet.
The absence of a spike in the cohort vaccinated in 2002-3 is still quite fatal, whether you're looking for it in 2002-3 or 2004-5, but there's a bit more to it than you described.
Prometheus,
RE: "Group W" bench
Yes, sir, Officer Obie, I cannot tell a lie, I put that envelope
under that garbage.
Wouldn't this hypothesis imply that infants who suffered HiB and didn't die would have a disproportionately high rate of autism? It seems to me that one would report that as supporting data in such a paper. Oh, wait...
So if Medical Hypotheses was peer-reviewed when Richmand's article was published, what peers should have reviewed it?
Richard Barr and the U.K. Legal Services Commission would have been naturals for the job.*
Hypothetically speaking, of course.
*apologies for the Wakefield humour.
palindrom @11: Actually, once you've shown pi is 3.125, you can then go on to show that any two numbers are equal. Inconsistencies allow that sort of thing in math.
That'd sure make it easier to do math! You could simply assert that any answer you dreamed up was correct!
And if you started doing that, Orac would probably write a column about you, since asserting that dreamed-up stuff is correct seems to be pretty much standard practice among his targets.
I always did like that pi = root 10 guy, though. Somehow, there's no crank quite as cranky as a math crank, since what they believe is so provably wrong, even without reference to any empirical data.
Every so often somebody'll come up with an apparent proof that 1=0, or the equivalent, and the rest of the math community then proceeds to find the flaw in it. The result, if it were concluded there is no flaw (which has never happened), would be that it would be necessary to introduce some new axiom in order to have an internally consistent system.
But it's a real thing. Sure cranks do it, but so do serious mathematicians. Kind of like the FTL neutrinos, really - "I got this result, it's probably not right, but I'll publish it so the rest of the community can find the problem. And maybe there's some outside chance that it's really right, which would be really exciting."
After reading herr doctor bimmler I just had to go and see if my Uni has access to the MH. And we do :: headdesk::
Tomorrow I will most definitely check if we pay for that privilege and if we do there will be questions asked you can bet on it.
@ Dangerous Bacon:
An apology? But we always like to joke about whatever is irksome, frightening, or truly despicable. It is a healthy way of coping with the dark side of reality- death, taxes and the gallows.*But* this turn of events is also poetically *just*! I have had a very long day that is not over yet: news like this made it easier.
Hi guys.
Thanks for the feedback.
I want to start off by stating that I am not one of the anti-vaccine cracks. A person would have to be insane not to readily see that vaccines have saved countless millions of lives.
I share the concern of many that parents acted irresponsibly in withholding vaccines from their children due to unfounded claims that the MMR vaccine or Thimerosal caused autism. Accordingly, I was careful to state that the paper should not be viewed as an indictment of the Hib vaccine and I detailed the importance of conjugate vaccines. However, we really need to be extremely cautious when it comes to conjugates (my view).
I disagree that the hypothesis is inconsistent with the McDonald paper. His paper was done by birth cohorts, so the results would not have started to be seen 5 years later.
You are correct that reported ASDs have continued to rise. However, I do not believe that ascertainment bias would account for all of the observed increase and a true increase and ascertainment bias are not mutually exclusive. Why after the definition of ASDs was modified in the early 1990s did we not see a rise in kids born in 1986 who were subsequently diagnosed with ASDs? The epidemiology of ASDs is a morass.
I apologize for my training in law and finance. However, I did also study immunology and have designed several studies at two medical schools looking at the immunologic and biochemical aspects of tic syndromes. Hardly an expert, but not a neophyte either.
The paper was reviewed by highly respected researchers at 4 leading U.S. medical schools prior to submitting to Medical Hypotheses. In some cases, these researchers spent multiple hours with me. Almost universally, the view was that the hypothesis was worthy of further study. A few people felt that the last thing we needed was another vaccine/ASD hypothesis. I also understand their (your) views.
Let me end by saying that the paper should not be tainted simply because it may be used as fodder by the anti-vaccine crowd. I saw in one place it was called a "study" (ouch!)
Respectfully,
Brian Richmand
do you mean this danish study?
"SILVER SPRING, Md., Oct. 25, 2011 /PRNewswire-USNewswire/ -- The Coalition for Mercury-free Drugs (CoMeD) exposes communications between Centers for Disease Control (CDC) personnel and vaccine researchers revealing U.S. officials apparently colluded in covering-up the decline in Denmark's autism rates following the removal of mercury from vaccines.
Documents obtained via the Freedom of Information Act (FOIA) show that CDC officials were aware of Danish data indicating a connection between removing Thimerosal (49.55% mercury) and a decline in autism rates. Despite this knowledge, these officials allowed a 2003 article to be published in Pediatrics that excluded this information, misrepresented the decline as an increase, and led to the mistaken conclusion that Thimerosal in vaccines does not cause autism. "
http://www.prnewswire.com/news-releases/scandal-exposed-in-major-study-…
Oooh, it is a press release!! From no less those fun guys in Maryland that have been chemically castrating children and are under investigation by the medical board. One has had his license suspended and another has been caught practicing medicine without a license. The CoMeDy continues.
"someone", why do you want haemophilus influenzae type b to return?
Someone,
That heavily redacted email has been discussed here already. It isn't clear what it shows, if anything.
The Madsen article published in 2003 found an increase in autism incidence for all age groups between 1990 and 1999 (Figure 1). Incidence in 5-9 year-olds fell between 1999 and 2000, but continued to increase in younger children. The email presumably refers to the older children, as it says "the incidence and prevalence are still decreasing in 2001".
Since thimerosal was removed from Danish vaccines in 1992 this means that some of these older children were exposed to thimerosal, but none of the younger ones were. This email suggests that autism incidence continued to decrease only in those children who received vaccines with thimerosal. I don't see how that supports the conclusion that thimerosal causes autism, quite the opposite if anything.
Really, someone, why do you want haemophilus influenzae to return? From Impact of Vaccines Universally Recommended for ChildrenâUnited States, 1900-1998:
And don't forget this Danish study:
JAMA. 2003 Oct 1;290(13):1763-6.
Association between thimerosal-containing vaccine and autism.
Hviid A, Stellfeld M, Wohlfahrt J, Melbye M.
I would like to propose not to wait until you earn enough amount of money to buy goods! You should get the loan or student loan and feel yourself free
Oh, goody. An anti-vaccine press release so bad that Chuck Norris embraced it:
http://scienceblogs.com/insolence/2011/11/chuck_norris_outdoes_jenny_mc…
@Brian Marchand
I'd be oh-so-curious which "respected scientists" thought that your hypothesis was worthy of further study, given how ethereal the evidence is to suggest that it's even slightly plausible.
Mr. Richmand:
Then why do you want haemophilus influenzae to return?
Surely in all of your medical studies you encountered something like relative risk? Do you not have any concept of how terrible a disease the Hib vaccine protects against?
And read what Orac said carefully, it is not only tainted because the anti-vax crowd embraces it: it is tainted because you used cherry picking. I suggest in your next comment you will elaborate why you only chose three countries, a link to the graphs you prepared but failed to include in your paper and why you cited McDonald and Paul.
Why would suggesting a study on a possible link between Hib and ASDs be the equivalent of wanting Hib to return. If there was an association it is not likely that all of the epitopes targeted by the vaccine would cross react with neural tissue. The vaccine could be modified. Also, the age of administration could possibly be adjusted. Lots of options.
How could you do a cost benefit analysis if you don't know what the risk is?
If I had another child, I would certainly vaccinate him against Hib based on the little we know, but I'd prefer that we have done post-marketing surveillance (as we now do with most drugs) to know that we were giving the safest formulation.
I don't know if you read the paper, but I could not have been clearer that I think Hib is serious (and I cite the statistics to back that up) and merely feel we need to carefully monitor conjugate vaccines. I can't be responsible if the clear language in the paper is mis-interpreted.
Although no one in my family has an ASD, I know several families with kids with autism disorder and can tell you that their lives are severely affected. Similarly, Hib can cause death, mental retardation and hearing loss. Those families are equally affected,
1987 is not a "change point" year.
The McDonald and Paul analysis of the CDDS data is flawed. Seriously flawed. Leaving behind all the limitations of using CDDS data, they fit data from the publications (scanned graphs?) to a simple two-line model. There is no reason to expect the data to be linear, or two linear regions. In fact, it is not.
Mr. Richmond,
From where I sit, one of what you consider a primary "strength" in your hypothesis relies upon what I believe to be a flawed result in what otherwise would, at best, be a weak paper.
As Orac points out, your description of immunology is missing a key feature--some tie in to autism.
I realize that you put this forth as a "hypothesis", but I hope you realize that the harm that the vaccine-causation groups have caused to not only public health, but to the autism communities has been substantial. It is hard to see the value in putting forth fodder for the likes of Mercola.
Matt Carey: The "value" for Mr. Richmand may be in telling it like it is. Some people actually do that, you know. I don't know whether you have noticed lately but the public's appetite for swallowing bullshit seems down.
Sick sauce:
But you seem to be gobbling it up.
Sick Sauce,
a "hypothesis" is, by definition, not "telling it like it is".
I agree that the public's appetite for swallowing bullshit is down. I doubt you will agree, but the public is no longer clambering for Jenny McCarthy to shout down professionals and throw out unproven or disproved hypotheses on vaccines and autism.
I "tell it like it is". The McDonald paper is in error about the changepoints in the CDDS data. I see you didn't even want to pursue that assertion. So I find it difficult to believe you want to "hear it like it is".
The change point did not occur prior to the use of the Hib vaccine in the US. The 1987 change point related to the 1987 birth cohort. When the vaccine was introduced in 1988, 15 month olds (who were part of the 1987 birth cohort) received the vaccine.
When the vaccine was introduced in 1993 in Denmark, they had a very aggressive catch up program so kids in the 1988 birth cohort were vaccinated. The was well within the confidence interval of the change point suggested by McDonald.
Three studies were chosen because they only used autism disorder, as opposed to ASDs. That was done to control for the change in the definition of ASDs (e.g., inclusion of Asperger's, PDD-NOS).
If you do not believe that autism disorder (which has had a more stable definition over time) has been increasing since the late 1980s, then there is no reason for you to consider the hypothesis. We just disagree.
The likely immunological tie to autism is the apparent perturbations in myelination seen in autism. Elucidation of this will require studies. Once possibility is that during the early myelination process there are some adhesion molecules that are only expressed in early brain development (and regulate the myelination process) that have been shown to cross-react to antibodies carbohydrate antigens expressed by capsular bacteria.
I will sign off now. We can agree to disagree whether this hypothesis deserves further study. There are several prominent researchers at major medical schools that agree that it does. I will defer to them rather than this group.
You keep saying that, but somehow you never manage to name any of these people. Sure, Noel R. Rose wrote an editorial for you, but his reasoning was almost as bad as yours and he was guilty of having a mind so open his brains fell out.
How disrespectful you guys are. Bunch as f'ing a-holes! Have fun with your circle jerk!
Mr. Richmand:
That is still cherry picking, especially since the DSM-IV came out in 1994. And it is kind of silly to try to show that a particular vaccine causes autism, when studies done in several countries failed to find a connection. Perhaps you were not familiar with the following papers:
Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism.
Price CS, Thompson WW, Goodson B, Weintraub ES, Croen LA, Hinrichsen VL, Marcy M, Robertson A, Eriksen E, Lewis E, Bernal P, Shay D, Davis RL, Destefano F.
Pediatrics. 2010 Sep 13.
Pediatrics. 2010 Jun;125(6):1134-41. Epub 2010 May 24.
On-time vaccine receipt in the first year does not adversely affect neuropsychological outcomes.
Smith MJ, Woods CR.
Pediatrics. 2010 Jun;125(6):1134-41. Epub 2010 May 24.
Neuropsychological Performance 10 years after Immunization in Infancy with Thimerosal-Containing Vaccines
Authors: Tozzi AE, Bisiacchi P, Tarantino V, De Mei B, D'Elia L, Chiarotti F, Salmaso S.
Source: Pediatrics, February 2009, Vol. 123(2):475-82
Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links with Immunizations.
Fombonne E et al.
Pediatrics. 2006;118(1):e139-50
Continuing Increases in Autism Reported to California's Developmental Services System: Mercury in Retrograde
Schechter R, Grether JK
Arch Gen Psychiatry, January 2008; 65(1):19-24
Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
Thompson WW, Price C, Goodson B, et al; Vaccine Safety Datalink Team
N Engl J Med, Sep 27, 2007; 357(13):1281-1292
Thimerosal Exposure in Infants and Developmental Disorders: A Prospective Cohort Study in the United Kingdom Does Not Support a Causal Association
Heron J, Golding J, ALSPAC Study Team
Pediatrics, September 2004, Vol. 114(3):577-583
Thimerosal Exposure in Infants and Developmental Disorders: A Retrospective Cohort Study in the United Kingdom Does Not Support a Causal Association
Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B
Pediatrics, September 2004, Vol. 114(3):584-591
Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Databases
Verstraeten T, Davis RL, DeStefano F, et al
Pediatrics, November 2003, Vol. 112(5):1039-1048
Association Between Thimerosal-Containing Vaccine and Autism
Hviid A, Stellfeld M, Wohlfahrt J, Melbye M
Journal of the American Medical Association, October 1, 2003, Vol. 290(13):1763-6
Mercola left out Hib causing epiglottitis, which is huge. It's one of those things that gets impressed upon you during peds rotations, cuz if you catch it quick enough you can save a little kid's life and if you miss it the kid will obstruct his airway and die.
Mercola is older than me, so I don't get why he doesn't feel that, "holy shit epiglottitis" reflex in response to "H. flu" or "Hib."
Orac, I believe that the sock puppet has decided to pretend to be Mr. Richmand.
Nope. It appears to be Richmand and not a sock puppet.
@Orac
Really? You'd think that having studied law, presumably also having practiced it, and been involved in some studies, he'd have a bit of a thicker skin and be able to take some well-reasoned criticism and snark.
Anti-vaccine activists frequently use very similar language in order to try to give the appearance that they are not "anti-vaccine." The mere fact that you used such language does not inoculate you from charges of being anti-vaccine. Whether you are or not, I have no idea, but the overall tone of your paper came across as at least borderline anti-vaccine, mainly because you used the same sort of fallacious arguments and cherry picking of studies that anti-vaccine activists do to make your point.
In addition, it's not our fault that you are apparently utterly unaware of how your arguments would be perceived, given that blaming vaccines for autism is a classic canard promoted by the anti-vaccine movement, particularly since it's a canard that has been well and conclusively refuted by science.
Let's suspend disbelief for a second and ignore atrocious immunology in the "hypothesis", if adjuvants increase immune response and sensitization to myelin wouldn't you see a significant increase in MS or any demyelinating lesions occurance?
Wow. Brian J Richmand Esq. stomps off in a foul-mouthed huff after some rather mild criticism of his paper.
Something else though occurred to me that further weakens the paper. Richmand wrote:
Richmand assumes that the distinction between autism disorder and the other elements of the spectrum (Asperger's, PDD-NOS) are always real and valid.
Apparently, not so:
Yes, the Lord study above came out after Richmand had done his research, but it really isn't anything surprising who is familiar with autism. If memory serves correctly, Grinker wrote about this phenomenon in Unstrange Minds, which has been out for almost 5 years.
I think Happé refers to the fluidity between the categories as "carving meatloaf at the joints".
So in addition to being thin-skinned, Mr. Richmand appears quite naive about autism.
Methinks Mr. Richmand has never encountered substantive criticism of his rather curious (and very wrong) ideas with regard to the Hib vaccine and autism. In any case, if his paper is any indication, he has just enough scientific training to be dangerous, so to speak, but not enough to have more than a superficial understanding of what he's talking about, which is, of course, what makes him dangerous.
That's actually him, stooping to profanity as he chides us for disrespect? Good grief. He seemed so rational before that. I disagreed with him, but goodness, if this is his reaction for people expressing a contrary opinion and asking about perceived weaknesses in his claims, I have to wonder if he has any more basis for his work than the fellow with the latex obsession.
Mr Richmand, Orac and others pointed out that 1987 was not a change point in diagnosis of autism. Yet you responded by saying "The change point did not occur prior to the use of the Hib vaccine in the US. The 1987 change point related to the 1987 birth cohort. When the vaccine was introduced in 1988, 15 month olds (who were part of the 1987 birth cohort) received the vaccine." Whether it occurred prior to the use of HiB vaccine is immaterial if the change point does not actually exist. I think you should be prepared to defend your claimed change point if you want your argument to hold water.
Convincing people here would be good, but we're a small bunch. It's the world you really need to convince. Consider this a very small-scale and relatively polite* avenue for testing your defense of your claims. Now, you don't actually have any obligation to defend your claims. It all depends on how much confidence you have in them.
*Yes, polite; note that you were the first to resort to veiled profanity and vulgar metaphors. You will not find the court of public opinion to be so kind, and while academia generally avoids the vulgarities and outright name-calling, they will not shy away from pointing out errors or weaknesses. Quite the contrary, in fact; they'll attack it with relish, since that's how it works.
Oh, wow. Mr. Richmand is starting to remind me of someone else who has an obsession with rubber.
Is it bad for me to say that I had a good laugh at brian richmand's little temper tantrum?
titmouse:
See my now out of moderation comment, it is #12 and posted at November 17, 2011 2:22 PM.
I would also ask Mr. Richmand, what he proposes to do about the Hib vaccine? And perhaps what prompted him to go down this line of investigation.
Mr. Richmand,
I saw your assertion in your paper and the McDonald and Paul paper about the definition of autism being more stable in administrative data.
It isn't true. First off, one must accept the fact that the CDDS client base does not include everyone with autism, or even autistic disorder. One must meet the inclusion criteria. These changed significantly in the early 2000's. Just to provide a clear example of such a change.
The work of Peter Bearman's group has shown that what is defined as "autism" by the CDDS has, indeed, changed and changed over the time period you are concerned with.
You can "sign off" and listen only to those who agree with you, or you can listen and learn. Yes, there will be noise in the discussion.
(before I finished this I see that you have more than signed off...)
The Law, according to Brian Richmand:
When you have the facts, pound the facts.
When you don't have the facts, pound the Law.
When you have neither the facts nor the Law, call 'em a "Bunch as(sic) f'ing a-holes".
palindrom @11: Actually, once you've shown pi is 3.125, you can then go on to show that any two numbers are equal. Inconsistencies allow that sort of thing in math.
And in medicine. Bend the rules of evidence to allow homeopathy, and anything becomes possible.
The Law, according to Brian Richmand:
When you have the facts, pound the facts.
When you don't have the facts, pound the Law.
When you have neither the facts nor the Law, call 'em a "Bunch as(sic) f'ing a-holes".
To me dude smells moar like, "Don't ever defend. Always attack" -- a Hubbarism that has infected large sectors of the woo world.
The proper counter argument to the above is: "He mad."
How disrespectful you guys are. Bunch as f'ing a-holes! Have fun with your circle jerk!
Mr. Richmand, have you ever been inside a courtroom? And if you have, is that how you behave?
Good grief, I had more heat in an engineering meeting where I had to explain that truck gear do not shimmy (that means the big main landing gear of aircraft do not shake about) than you have had here. And all I had to do was show the data.
Dude, grow a backbone.
@Prometheus Here I thought I was the only one that still used the "Group W" bench!
With regards to why epidemiologists love to use Danish data - the Medical and Health registries over here are fantabulous - pretty much an epi's wet dream with regards to recordkeeping.
(That might tie into the whole masturbation as a cure for nasal issues, too!)
I still get a giggle when the anti-vaccine camp calls Statens Serum Institute "Big Pharma" - since it's essentially the Danish CDC.
@Tartu85, yes you would. Furthermore, decreased myelination is not a consistent finding among autistic brains and most importantly, such structural changes/abnormalities occur during in utero or pre-natal development, not months post-natally as his "hypothesis" states.
Chris, you cited a Fombonne study, pretty desperate, eh? Gosh golly Callie: why don't you worry more about jerk nurse and doctors vaccinating sick people, which I recall you speaking about quite strongly at one point- calling it "off-label." I mean you are obviously wanting people to get vaccinated and yet not get injured by them so I think this would be a great area for you to advocate and use your voice for good. JM2C.
A- nonymous, did you miss the all of the other studies?
The evidence that vaccines are not related to autism is not based on one study, but the collection of studies. As you can see, the data does not support a connection between vaccines and autism.
And you are back! Hurray! Have you finally found the answer to the question I keep asking you during the last two months?
So, exactly which vaccines cause more seizures than the diseases? Please provide the body of work showing that a vaccine on the present pediatric schedule is responsible for more seizures than the disease.
***"How disrespectful you guys are. Bunch as f'ing a-holes! Have fun with your circle jerk!"
It seems that in addition to having (some) education in "immunology", our potty-mouthed lawyer has also studied "profanity".
Does Richmand use these same words when he represents clients in court, or around the wealthy suburban New York State town where he resides?
***We were assuming that a member of the bar who publishes a paper about HIB vaccine linked to increased diagnoses of autism, would honestly defend the paper.
Thanks Orac, for busting this guy.
Chris is absolutely correct: We cannot study vaccine safety because if we do all killer diseases will return.
And now, Ladies and Gentlemen, this is the time for Friday's Educational Minute.
Today's topic, the Strawman fallacy.
Please applaud Mr Sid, who kindly accepted to give us a free demonstration.
Thank you Mr Sid, it was masterful. The exit is this way.
@ Heliantus: I thought Offal was finished commenting here...after the derision heaped upon him about his "credentials" as a college graduate with a "fire science" degree.
Note to Offal: I listened to your radio "debut" on BBC Radio 5 Live...it was not an "auspicious" moment for you. Just keep your day job, Offal.
@baglady
Sorry for beating Dr. Schaffner like a rented mule.
Sorry for beating Dr. Schaffner like a rented mule.
Ah, it was foreplay.
Ah delusions of grandeur with a healthy dose of Dunning-Kruger, a pre-requisite of an anti-vax mouthpiece. Do tell how you "beat Dr. Schaffner like a rented mule" Sid because I can certainly see how you did "masturbate violently and prolifically" (see Urban Dictionary).
Offal...you made a fool of yourself with your dopey Randian libertarian comments on the BBC radio program. Dr. Schaffner whupped your a**.
You should stick to your "day job"...whatever that is...and your blog.
It's incredible how many people have taken the "hypotheses" in that journal very seriously and equated it as fact. An all too common fallacy among the laymen is that if it's in a medical journal, therefore it's fact.
"Medical Hypotheses" has "medical" in it, but it's not a medical journal. It's too moonbatty.
Whoops, I forgot to put quotations on "medical journal" on my last comment. But anyway, if the words "statistically significant", "medical", "science/scientific method", "journal" or "conclusion" are involved, many laymen automatically think it's legitimate. *Especially* with "statistically significant" and "scientific method".
@ titmouse & Don't Touch: Your comments about the Medical Hypotheses Journal are very similar to what the editors of the publication state:
"Medical Hypotheses is a forum for ideas in medicine and related biomedical sciences. It will publish interesting and important theoretical papers that foster the diversity and debate upon which the scientific process thrives. The Aims and Scope of Medical Hypotheses are no different now from what was proposed by the founder of the journal, the late Dr David Horrobin. In his introduction to the first issue of the Journal, he asks 'what sorts of papers will be published in Medical Hypotheses? and goes on to answer 'Medical Hypotheses will publish papers which describe theories, ideas which have a great deal of observational support and some hypotheses where experimental support is yet fragmentary'. (Horrobin DF, 1975 Ideas in Biomedical Science: Reasons for the foundation of Medical Hypotheses. Medical Hypotheses Volume 1, Issue 1, January-February 1975, Pages 1-2.). Medical Hypotheses was therefore launched, and still exists today, to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals. Papers in Medical Hypotheses take a standard scientific form in terms of style, structure and referencing. The journal therefore constitutes a bridge between cutting-edge theory and the mainstream of medical and scientific communication, which ideas must eventually enter if they are to be critiqued and tested against observations.
Submitted manuscripts will be reviewed by the Editor and external reviewers to ensure their scientific merit. All reviewers will be fully aware of the Aims and Scope of the Journal and will be judging the premise, originality and plausibility of the hypotheses submitted."
Really "good" articles that are published in their journal may be eligible for the "Horrobin Prize"...1000 pounds sterling awarded yearly by the editors.
Sick sauce @36
Your comment is not consistent with popularity of certain presidential candidate hopefuls.
Oh dear FSM - my uni library does subscribe (via ScienceDirect) to MH! I have written to the science librarian to see if we can get shot of it. I've previously warned my students about citing work in it as relaible evidence in support of an argument, but I never would have thought that we actually subscribed to it :-(.
In the whole history of MH, has it ever published a "hypothesis where experimental support is yet fragmentary" that turned out to actually be correct? It seems to me that whatever function MH once served is now completely redundant with the rise of the Internet, and completely outweighed by the dysfunction it serves of helping crankery camouflage itself as part of the scientific discourse.
The Medical Hypotheses Editorial Board includes some surprisingly respectable people. I quite like the journal, I think of it as the medical equivalent of Fortean Times, to be read for entertainment value and the odd interesting idea, but not to be taken too seriously. I don't think it should be listed on PubMed and I don't think it should make itself look so much like a mainstream medical journal.
I think of it as the medical equivalent of Fortean Times, to be read for entertainment value and the odd interesting idea, but not to be taken too seriously.
Annals of Improbable Research, but with a more subtle sense of humour?
This is great. Iâve been looking at the results - you must be porud!